Rebecca Swayngim, PharmD, BCCCP,
Critical Care Pharmacist
Denver Health Medical Center
Denver, CO
Disclosure information not submitted.
.jpg "Candice Preslaski, BCCCP, PharmD photo")
Candice Preslaski, BCCCP, PharmD
Surgical Critical Care Specialist
Denver Health
Denver, CO
Disclosure information not submitted.
Jordan Dawson, BCPS, PharmD, BCCCP
Pharmacist
Denver Health, United States
Disclosure information not submitted.
Title: Use of Valproic Acid for Agitation and Delirium in the Intensive Care Unit
Introduction:
Delirium and agitation are common occurrences in patients admitted to the intensive care unit (ICU). Delirium has been associated with higher mortality, increase length of stay (LOS), and long-term cognitive impairment. Multiple antipsychotics used to mitigate delirium and/or agitation in the ICU have been evaluated without improvement in duration of delirium. Valproic acid (VPA) is a potential alternative that targets many of the pathways implicated in the pathophysiology of delirium, however, there is a paucity of robust data to consistently support its use.
Methods:
This was a retrospective cohort study of patients treated for delirium and agitation admitted to the medical ICU and surgical/trauma ICUs at Denver Health Medical Center from January 1, 2016 to October 1, 2020. Patients were included if they had a Richmond Agitation-Sedation Scale (RASS) ≥ 2, were Confusion Assessment Method for the ICU (CAM-ICU) positive and received antipsychotic medications during their ICU stay. Patients were excluded if they received VPA prior to admission or for non-study indications. Patients were split into two groups based on their VPA exposure. The primary outcome was delirium and coma free days at 14 days or ICU discharge. Secondary outcomes included agitation and coma free days at 14 days or ICU discharge, ICU LOS, mechanical ventilation duration, in hospital and 28-day mortality. Descriptive and safety data were also collected for the VPA group.
Results:
108 patients were included, 49 patients in the VPA group and 59 patients in the no-VPA group. Baseline characteristics were similar between groups. There was no significant difference in the primary outcome (difference -0.15, 95% CI 0.63-0.93, p=0.70). There were no significant differences in agitation-free days, in-hospital mortality, 28-day mortality, duration of mechanical ventilation, or ICU LOS. In the VPA group, hepatotoxicity occurred in 6.12% of patients, thrombocytopenia in 12.24% and there was no laboratory evidence of hyperammonemia.
Conclusions:
Our findings suggest that VPA is associated with similar delirium and agitation-free days compared to other antipsychotics. Larger, prospective, controlled studies are needed to validate the routine use of VPA for the treatment of delirium and agitation in the ICU.